UNASSIGNED: Overweight and obesity have been found to exhibit a statistically significant increase in corrected QT interval (QTc), a major contributing factor to sudden death. However, the influence of widely used weight loss strategies including diet, exercise, anti-obesity drugs, and bariatric surgery on QTc remains inconsistent. Therefore, the present systematic review and meta-analysis aim to quantitatively analyse and evaluate the effect of weight loss on QTc in obese patients after diet control with exercise intervention and anti-obesity drugs, as well as bariatric surgery.
UNASSIGNED: Twenty randomised controlled trials (RCT) and observational studies were included in the meta-analysis on the effects of weight loss on QTc. The fixed-effects model was employed in the RCTs, and the random-effects model was employed due to the presence of statistical heterogeneity among observational studies. Subgroup analysis was conducted to understand the differences in distinct weight loss methods and follow-up time.
UNASSIGNED: Overall, the QTc of people with obesity after weight loss was shorter than that before (mean difference (MD) = 21.97 ms, 95% confidence interval (CI) = 12.42, 31.52, p < .0001). Subgroup analysis restricted to seven included studies whose intervention was diet control with exercise showed a decrease of QTc with statistical significance (MD = 9.35 ms, 95%CI = 2.56, 37.54, p = .007). In the remaining 11 studies, bariatric surgery was the weight loss method. The results also showed a shortening of QTc after surgery, and the difference was statistically significant (MD = 29.04 ms, 95%CI = -16.46, 41.62, p < .00001). A statistically significant difference in QTc shortening at 6 months compared to pre-operation values was further observed (MD = -31.01 ms, 95%CI = -2.89, -59.12, p = .03). The shortening of QTc at 12 months of follow-up was also significantly different from that before surgery (MD = 36.47 ms, 95%CI = 14.17, 58.78, p < .00001). Moreover, the differences became more pronounced as the follow-up time extended.
UNASSIGNED: We demonstrate that weight loss links to a shortened QTc, without considering the means of weight loss. Bariatric surgery has been found to result in a greater reduction in QTc.

Escitalopram can cause prolongation of the QT interval on the electrocardiogram (ECG). However, only some patients get pathological QTc prolongation in clinic. We investigated the influence of KCNQ1, KCNE1, and KCNH2 gene polymorphisms along with clinical factors on escitalopram-induced QTc prolongation.
A total of 713 patients prescribed escitalopram were identified and had at least one ECG recording in this retrospective study. 472 patients with two or more ECG data were divided into QTc prolongation (n = 119) and non-prolongation (n = 353) groups depending on the threshold change in QTc of 30 ms above baseline value (∆QTc ≥ 30 ms). 45 patients in the QTc prolongation group and 90 patients in the QTc non-prolongation group were genotyped for 43 single nucleotide polymorphisms (SNPs) of KCNQ1, KCNE1, and KCNH2 genes.
Patients with QTc prolongation (∆QTc ≥ 30 ms) got higher escitalopram dose (10.3 mg) than patients without QTc prolongation (9.4 mg), although no significant relationship was found between QTc interval and escitalopram dose in the linear mixed model. Patients who were older/coronary disease/hypertension or carried with KCNE1 rs1805127 C allele, KCNE1 rs4817668 C allele, KCNH2 rs3807372 AG/GG genotype were significantly at risk for QTc prolongation (∆QTc ≥ 30 ms). Concomitant antipsychotic treatment was associated with a longer QTc interval.
A relatively small sample size and lack of the blood concentration of escitalopram restricted the accurate relationship between escitalopram dose and QTc interval.
Our study revealed that KCNQ1, KCNE1, and KCNH2 gene polymorphisms along with clinical factors provide a complementary effect in escitalopram-induced QTc prolongation.

The predictive utility of QTc values, calculated through various correction formulas for the incidence of postoperative major adverse cardiovascular and cerebrovascular events (MACCE) in patients experiencing acute myocardial infarction (AMI), warrants further exploration. This study endeavors to ascertain the predictive accuracy of disparate QTc values for MACCE occurrences in patients with perioperative AMI.
A retrospective cohort of three hundred fourteen AMI patients, comprising 81 instances of in-hospital MACCE and 233 controls, was assembled, with comprehensive collection of baseline demographic and clinical data. QTc values were derived employing the correction formulas of Bazett, Fridericia, Hodges, Ashman, Framingham, Schlamowitz, Dmitrienko, Rautaharju, and Sarma. Analytical methods encompassed comparative statistics, Spearman correlation analysis, binary logistic regression models, receiver operating characteristic (ROC) curves, and decision curve analysis (DCA).
QTc values were significantly elevated in the MACCE cohort compared to controls (P < 0.05). Spearman\'s correlation analysis between heart rate and QTc revealed a modest positive correlation for the Sarma formula (QTcBaz) (ρ = 0.46, P < 0.001). Within the multifactorial binary logistic regression, each QTc variant emerged as an independent risk factor for MACCE, with the Sarma formula-derived QTc (QTcSar) presenting the highest hazard ratio (OR = 1.025). ROC curve analysis identified QTcSar with a threshold of 446 ms as yielding the superior predictive capacity (AUC = 0.734), demonstrating a sensitivity of 60.5% and a specificity of 82.8%. DCA indicated positive net benefits for QTcSar at high-risk thresholds ranging from 0 to 0.66 and 0.71-0.96, with QTcBaz, prevalent in clinical settings, showing positive net benefits at thresholds extending to 0-0.99.
For perioperative AMI patients, QTcSar proves more advantageous in monitoring QTc intervals compared to alternative QT correction formulas, offering enhanced predictive prowess for subsequent MACCE incidents.

OBJECTIVE: To analyze the clinical and genetic characteristics of a patient with long QT syndrome type 14 (long QT syndrome-14, LQT14, OMIM # 616247) caused by a de novo CALM1 mutation.
METHODS: The clinical data of the patient were collected, next-generation sequencing technology was used to determine the exome gene sequence of the patient, and the suspected pathogenic locus was verified by Sanger sequencing.
RESULTS: A 5-year and 9-month-old girl was admitted to the hospital due to a syncopal episode. During the attack, the main symptoms were loss of consciousness, cyanosis of the face and lips, and weakness of limbs. The child had multiple seizures in the past, all of which occurred after emotional excitement and activity. She was diagnosed with epilepsy for more than 3 years, but the effect of antiepileptic treatment was not satisfactory. The electrocardiogram was normal in the past. A month ago, convulsions occurred again after exercise, and the electrocardiogram showed QTc 496 ms. The treadmill test showed a significant prolongation of QTc after exercise, and the genetic results suggested a new heterozygous variant of CALM1, c.395A>G; p. (Asp132Gly). Consequently, she was diagnosed with LQT14 and treated with propranolol. During a follow-up of 15 months, there were no seizures or syncope.
CONCLUSIONS: This patient had multiple episodes of convulsions or syncope after emotional stimulation or activity, with intermittent prolongation of the QTc on routine ECG, marked prolongation of the QTc after exercise, and T-wave alternans, which differed from the LQT14 phenotype caused by the previous CALM1 mutation.

UNASSIGNED: Systemic immune inflammatory index (SII) and systemic inflammatory response index (SIRI) are combinations of non-specific inflammatory and adaptive immune response impairments associated with cardiovascular disease. Yet little analysis has been done on SII, SIRI and acute myocardial infarction (AMI) prognosis. The purpose of this study was to investigate the correlation of SII and SIRI with clinical risk factors such as GRACE, Gensini, and QTc after acute myocardial infarction.
UNASSIGNED: This study enrolled 310 patients with AMI from February 1, 2018, to December 31, 2022, at our institution. Routine blood items calculated SII and SIRI. Two groups were divided according to whether MACE occurred: the MACE group (81 cases) and the NMACE group (229 cases); each group was divided into three groups according to the SII and SIRI tertiles. The relationship between SII, SIRI and MACE was analyzed using multifactorial logistic regression analysis after adjusting for confounders; ROC curves were plotted to examine the predictive value of SII and SIRI for MACE. The correlation between SII and SIRI and potential risk factors such as Gensini, QTc and GRACE was further analyzed.
UNASSIGNED: The study enrolled 310 patients, comprising 248 men (80%, mean age 60.73 ± 13.695 years) and 62 women (20%, mean age 69.79 ± 11.555 years). In the regression model completely adjusted for confounders, the risk of MACE was higher in AMI patients with SII > 11.00 [OR = 1.061,95% CI (1.018,1.105)] than in SII < 5.98; the risk of MACE was 115.3% higher in AMI patients with SIRI (1.72-3.68) [OR = 2.153, 95% CI (1.251, 3.705)] was 115.3% higher in AMI patients with SIRI < 1.72 and the risk of MACE was 25.1% higher in AMI patients with SIRI > 3.68 [OR = 1.251, 95% CI (1.123, 1.394)] than in AMI patients with SIRI < 1.72. In addition, SII, SIRI, and potential post-infarction risk factors (Gensini, QTc, and GRACE) were also associated.
UNASSIGNED: SII and SIRI have been significantly associated with post-myocardial infarction MACE and the predictive potential clinically integrated risk factors in AMI patients, for which more attention should be paid to targeted anti-inflammatory therapy in AMI patients to further reduce the incidence of prognostic MACE in AMI patients.

At present, there is not enough evidence to prove the relationship between blood lipid and electrocardiogram (ECG) abnormalities in common mental disorders (CMD). This study aimed to explore the relationship between them, to detect and prevent arrhythmia or sudden death.
We collected 272 CMD patients (maintained a fixed drug dose pattern for 1 year or more), including 95 schizophrenias (SC), 90 bipolar disorders (BD) and 87 major depressive disorders (MDD), and 78 healthy controls (HC) from the Third People\'s Hospital of Foshan, China. We analyzed and compared their blood lipid and ECG indicators, to clarify the relationship between them.
350 participants were included. There were no significant differences in age, gender, total cholesterol (TC), low density lipoprotein (LDL) and QTc (p > 0.05) among subjects. And there were significant differences in body mass index (BMI), triglyceride (TG), high density lipoprotein (HDL), heart rate, PR interval and QRS width (p < 0.05). Person correlation analysis showed that QRS width was positively correlated with BMI and TG. And negatively correlated with HDL. Meanwhile, QTc was positively correlated with BMI. Multiple linear regional analysis further proved that TG (B = 3.849, p = 0.007) and LDL (B = 11.764, p = 0.018) were the risk factors, and HDL (B = -9.935, p = 0.025) was the protective factor for QRS width increase.
Long term medication of CMD patients should strengthen weight management, and conduct regular blood lipid and ECG examinations to achieve early detection and intervention in order to promote their health.

OBJECTIVE: The full potential of methadone maintenance treatment (MMT) is often limited by the large inter-individual variability in both pharmacokinetics (PK) and pharmacodynamics (PD), and by the risk of torsade de pointes, a severe adverse effect caused by QTc prolongation. The current study aims to quantitate the contribution of genetic polymorphisms and other variables in PK/PD variability, and their contribution to the QTc interval prolongation in Chinese MMT patients.
METHODS: Population PK models were developed to fit (R)- and (S)-methadone PK data. Hierarchical models were tested to characterize the PK profile, the concentration-QTc relationship, and concentration-urinalysis illicit drug testing relationship, with demographics and genetic variants being included as covariates. Simulation based on the developed PK/PD models was performed to assess the effect of methadone dose and genetic variants on QTc interval prolongation.
RESULTS: The PK data were best-fit by a one-compartment, first-order absorption model. Clearance of (R)- and (S)-methadone was both affected by the weighted activity score derived from genetic variants. A linear model was used to describe both the methadone concentration-urinalysis illicit drug testing relationship and the methadone concentration-QTc relationship. Concentration of (R)- and (S)-methadone exhibits a comparable effect on QTc prolongation. Simulation showed that the percentage of QTc higher than 450 ms was almost doubled in the lowest clearance group as compared the highest when methadone dose was greater than 120 mg.
CONCLUSIONS: The large variability in PK/PD profiles can be partially explained by the genetic variants in an extent different from other population, which confirmed the necessity to conduct such a study in the specific Chinese patients.

β-Blockers are first-line therapy in patients with long QT syndrome (LQTS). However, β-blockers had genotype dependent efficacy (LQT1>LQT2>LQT3). Sodium channel blockers have been recommended as add-on therapy for LQT3 patients. However, the pooled effect of sodium channel blockers in all LQTS patients remains unknown.
We conducted a systematic electronic search of PubMed, Embase, and the Cochrane Library. Fixed effects model was used to assess the effect of sodium channel blockers on QTc, cardiac events (CEs), and the proportion of QTc ≥ 500 ms and QTc ≤ 460 ms in LQTS patients.
Pooled analysis of 14 studies with 213 LQTS (9 LQT1 + 63 LQT2 + 135 LQT3 + 6 others) patients showed that sodium channel blockers significantly shortened QTc by nearly 50 ms (mean difference [MD], -49.43; 95% confidence interval [CI], -57.80 to -41.05, p < .001), reduced the incidence of CEs (risk ratio [RR], 0.23; 95% CI, 0.11-0.47; p < .001) and the proportion of QTc ≥ 500 ms (RR, 0.33; 95% CI, 0.24-0.47; p < .001), and increased the proportion of QTc ≤ 460 ms (RR, 10.33; 95% CI, 4.62-23.09; p < .001). Sodium channel blockers significantly shortened QTc both in LQT3 and LQT2 patients, while the QTc shortening effect in LQT3 was superior to that in LQT2 (57.39 vs. 36.61 ms). Mexiletine, flecainide, and ranolazine all significantly shortened QTc, and the QTc shortening effect by mexiletine was the best (60.70 vs. 49.08 vs. 50.10 ms).
Sodium channel blockers can be useful both in LQT3 and LQT2 patients. Mexiletine, flecainide and ranolazine significantly shortened QTc in LQTS patients, and the QTc shortening effect by mexiletine was the best.

UNASSIGNED: Prolonged corrected QT (QTc) interval is a hallmark of cirrhotic cardiomyopathy (CCM) and has been ascertained to predict mortality in cirrhosis. However, some critical issues remain to be addressed including unanimous cut-off, calculation approach and applicable population.
UNASSIGNED: A total of 274 patients with cirrhosis were included. The prolonged QTc interval over 440 ms according to adjusted Fridericia\'s formula was used to stratify enrolled subjects. Independent predictors of 3-year mortality were identified with Cox regression model. The Kaplan-Meier method was implemented to obtain survival curves. To reduce impact of selection bias and possible confounders, a propensity score matching (PSM) analysis was used.
UNASSIGNED: QTc > 440 ms was an independent risk factor in the entire cohort and PSM subset (HR 2.532, 95% CI 1.431-4.480, p=.001; HR 2.802, 95% CI 1.171-6.701, p=.021, respectively). Subgroup analysis showed that QTc > 440 ms was an independent predictor in cirrhotics with age ≤60 years (HR = 1.02, p=.035) and in the presence of ascites (HR = 1.01, p=.008).
UNASSIGNED: The prolonged QTc interval might help to identify patients with high-risk of all-cause mortality.

The aim of this analysis was to investigate the potential for ulixertinib (BVD-523) to prolong cardiac repolarization. The mean prolongation of the corrected QT (QTc) interval was predicted at the mean maximum drug concentrations of the recommended phase 2 dose (RP2D; 600 mg BID) and of higher concentrations. In addition, the effect of ulixertinib on other quantitative ECG parameters was assessed.
In a two-part, phase 1, open-label study in adults with advanced solid tumors, 105 patients [24 in Part 1 (dose escalation) and 81 in Part 2 (cohort expansion)] were included in a QT prolongation analysis. Electrocardiograms (ECGs) extracted from 12-lead Holter monitors, along with time-matched pharmacokinetic blood samples, were collected over 12 h on cycle 1 day 1 and cycle 1 day 15 and analyzed by a core ECG laboratory.
A small increase in heart rate was observed on both study days (up to 5.6 bpm on day 1 and up to 7 bpm on day 15). The estimated mean changes from baseline in the study-specific QTc interval (QTcSS), at the ulixertinib Cmax, were - 0.529 ms (90% CI - 6.621, 5.562) on day 1 and - 9.202 ms (90% CI - 22.505, 4.101) on day 15. The concentration: QTc regression slopes were mildly positive but not statistically significant [0.53 (90% CI - 1.343, 2.412) and 1.16 (90% CI - 1.732, 4.042) ms per µg/mL for days 1 and 15, respectively]. Ulixertinib had no meaningful effect on PR or QRS intervals.
Ulixertinib administered to patients with solid tumors at clinically relevant doses has a low risk for QT/QTc prolongation or any other effects on ECG parameters.
The study is registered at Clinicaltrials.gov (NCT01781429) and was sponsored by BioMed Valley Discoveries.